pharmaceutical organic chemistry


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Combinatorial chemistry

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pharmaceutical organic chemistry

  2. 2. INTRODUCTION :*Combinatorial chemistry is one of the important new methodsdeveloped by academics and researchers in the pharmaceutical,chemical, and biotechnology industries to reduce the time andcosts associated with producing effective, marketable, andcompetitive new drugs. *Simply, scientists use combinatorial chemistry to create large populations of molecules, or libraries, that can be screened efficiently. * By producing larger, more diverse compound libraries, companies increase the probability that they will find novel compounds of significant therapeutic and commercial value. *The field represents: a convergence of chemistry and biology, made possible by fundamental advances in miniaturization, robotics, and receptor development. 2
  3. 3. * And not surprisingly, it has also captured the attention of every major player in the pharmaceutical, biotechnology, and agrochemical arena.*Technique invented in the late 1980s and early 1990s toenable tasks to be applied to many molecules simultaneously 3
  4. 4. DEFINITION :*Combinatorial chemistry is a technique by which large numbersof structurally distinct molecules may be synthesized in a timeand submitted for pharmacological assay.*The key of combinatorial chemistry is that a large range ofanalogues is synthesized using the same reaction conditions, thesame reaction vessels.*In this way, the chemist can synthesize many hundreds orthousands of compounds in one time instead of preparing only afew by simple methods . 4
  5. 5. In the past*chemists have traditionally made one compound at a time.*For example compound A would have been reacted withcompound B to give product AB, which would have been isolatedafter reaction work up and purification through crystallization,distillation, or chromatography.In contrast to this approach*combinatorial chemistry offers the potential to make everycombination of compound A1 to An with compound B1 to Bn.The range of combinatorial techniques is highly diverse, andthese products could be made individually in a parallel or inmixtures, using either solution or solid phase techniques.Whatever the technique used the common denominator is thatproductivity has been amplified beyond the levels that have beenroutine for the last hundred years. 5
  6. 6. TOOLS: - Solid-phase synthesis – Resins – Reagents (Monomers) – Linkers – Screening methods METHODS :1-Use of solid supports for peptide synthesis led to widerapplications2-Products from one reaction are divided and reacted with otherreagents in succession Benefits to material science :1-Combinatorial approaches now being applied to solid-state andmaterials applications2-Also to search for new catalysts 6
  7. 7. Application of Combinatorial Chemistry :*Applications of combinatorial chemistry are very wide.* For example in pharmaceutical companies for drug designs.For illustrate this, one a practical example:Transition-state analog HIV protease inhibitors.-Extensive efforts toward the rational design of aspartylprotease inhibitors such as renin and HIV have led to thediscovery of several transition-states analog mimics.-These templates can serve as the central unit around whichmolecular diversity can be generated by application ofappropriate chemistries.- Recently, solid phase synthesis of hydroxyethylamine and1,2-diol transition-state pharmacophore units and their utilityfor synthesis of HIV protease inhibitors have been reported bytwo different groups.-The first instance, bifunctional linker are used by Wang toserve the dual purpose of protecting the hydroxyl group ofthese BBs and providing point for attachment on solid support. 7
  8. 8. -Thus, one linker possesses a vinyl ether group at one end anda free carboxylate group at the other.-The vinyl ether moiety is reacted with diamino alcohol BB 1under acid-catalysed conditions to form an acetal protectinggroup and the carboxylic acid group is used for ester-typelinkage to the solid support. 8
  9. 9. -The other linker possesses a methyl ketone and carboxylicgroups at the two ends, with the ketone group forming a ketalwith diol 3.-Resulting intermediates 2 and 4 are now well suited for a bi-directional solid phase synthesis strategy for preparing C2symmetric HIV protease inhibitors.- The two terminal amino groups of 2 and 4 are deprotectedand reacted with a variety of carboxylic acid, sulfonyl chlorides,isocyanates, and chloroformates to extend the core unit in bothdirections and generate a wide variety of aspartyl proteaseinhibitors. 9
  10. 10. ADVANTAGES AND DISADVANTAGES : 1-ADVANTAGES:1-save time2-fast3-produce unexpected new compounds4-used in many biological & chemical applications5-save money 10
  11. 11. 2-DISADVANTAGES:1-Cant used with Many compounds had undesirable propertieslike – Size – Solubility – Inappropriate functional groups2-Early libraries often based on a single skeleton (basic structure)3-Limited number of skeletons accessible4-Individual library members were structurally similar5-Compounds tended to be achiral or racemic6-Initial emphasis on creating mixtures of very large numbers ofcompounds now out of favor 11
  12. 12. REFRENCES :1- html2- Chemistry-and-Library-Design4- MADE BY SECTION(2) :1- JehanEssam Mahmoud (112) .2- Aya Ahmed Saber Yosif (86).3- Eman Mohammed MostafaSherra (83).4- Eman Ahmed AlaaElshamy .5- AyaSamir . 12
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